Technical Abstract:
The 1918-1919 influenza virus pandemic is estimated to have caused more than 20 million deaths worldwide. We have generated recombinant influenza A viruses bearing the hemagglutinin (HA) and/or neuraminidase (NA) genes from the 1918 virus under biosafety level 3 agriculture conditions. Using the BALB/c mouse as mammalian model we investigated the pathogenesis and immunity to the 1918 HA/1918 NA:WSN recombinant virus. The 1918 HA/1918 NA:WSN recombinant virus was highly lethal for mice and resulted in uncontrolled replication in the lung tissue. Lung histology showed a more severe inflammatory cell infiltrate in alveoli and the presence of more severe necrosis of bronchial epithelial cells than was observed in lung tissue of mice infected with a recombinant virus possessing the HA and NA of influenza A/New Caledonia/20/99 (New. Cal. HA/New Cal. NA:WSN) virus. The protective efficacy of inactivated influenza A vaccines that represent early and more recent influenza H1N1 viruses were tested. Mice were vaccinated intramuscularly with 10 µg of purified inactivated vaccine and challenged with 100 LD50 of the 1918 HA/1918 NA:WSN recombinant virus. Mice vaccinated with the homologous 1918 HA/1918 NA:WSN vaccine were completely protected against death and infection (day 4 post-infection) following lethal challenge, whereas mice vaccinated with either A/Puerto Rico/8/34 or A/New Caledonia/20/99 vaccines were protected against death, but not from infection. In contrast, control mice which received an H3N2 (X-31) vaccine died 6 to 11 days post-challenge with high titers of infectious virus in the lung tissue. These results suggest that H1N1 virus vaccines may offer some degree of protection against an emergent 1918-like influenza virus.